Cough is one of the most important defensive reflexes. However, extensive non- productive cough is a harmful mechanism leading to the damage of human airways. Cough is initiated by activation of vagal afferents in the airways. The site of their convergence is particularly the nucleus of the solitary tract (nTS). The second-order neurons terminate in the pons, medulla and spinal cord and there is also the cortical and subcortical control of coughing. Upper airway cough syndrome (UACS) – previously postnasal drip syndrome - is one of the most common causes of chronic cough together with asthma and gastroesophageal reflux. The main mechanisms leading to cough in patients with nasal and sinus diseases are postnasal drip, direct irritation of nasal mucosa, inflammation in the lower airways, upper airway inflammation and the cough reflex sensitization. The cough demonstrated by UACS patients is probably due to hypersensitivity of the upper airways sensory nerve or lower airways sensory nerve, or a combination of both. Further studies are needed to clarify this mechanism.

Asthma is a complex disease with a variable course. Efforts to identify biomarkers to predict asthma severity, the course of disease and response to treatment have not been very successful so far. Biomarker research has expanded greatly with the advancement of molecular research techniques. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient. An ideal biomarker should be suitable to identify the disease as well the specific endotype/phenotype, useful in the monitoring of the disease and to determine the prognosis, easily to obtain with minimum discomfort or risk to the patient - exhaled breath analysis, blood cells and serum biomarkers, sputum cells and mediators and urine metabolites could be potential biomarkers of asthma bronchiale. Unfortunately, at the moment, an ideal biomarker doesn’t exist and the overlap between the biomarkers is a reality. Using panels of biomarkers could improve probably the identification of asthma endotypes in the era of precision medicine.

New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. The aim of this study was to clarify changes of cough reflex sensitivity – the activity of airway afferent nerve endings - in asthmatic children. 25 children with asthma and 15 controls were submitted to cough reflex sensitivity measurement - capsaicin aerosol in doubling concentrations (from 0.61 to 1250 µmol/l) was inhaled by a single breath method. Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Asthmatic children' (11 boys and 14 girls, mean age 9 ± 1 yrs) cough reflex sensitivity (geometric mean, with the 95 % CI) for C2 was 4.25 (2.25-8.03) µmol/l vs. control C2 (6 boys and 9 girls, mean age 8 ± 1 yrs) was 10.61 (5.28-21.32) µmol/l (p=0.024). Asthmatic children' C5 was 100.27 (49.30-203.93) µmol/l vs. control C5 56.53 (19.69-162.35) µmol/l (p=0.348). There was a statistically significant decrease of C2 (cough threshold) in the asthmatic patients relative to controls (p-value for the two-sample t-test of log(C2) for the one-sided alternative, p-value = 0.024). The 95 % confidence interval for the difference of the mean C2 in asthma vs. control, [1.004, 6.207]. For C5, the difference was not statistically significant (p-value = 0.348). There was a statistically significant decrease of cough reflex sensitivity (the activity of airway afferent nerve endings) - C2 value in the asthmatic children relative to controls.

Rhinosinusitis is one of the most common conditions in primary and secondary care all over the world. Rhinosinusitis together with asthma and gastroesophageal reflux disease represent the most common causes of chronic cough. The relationship between rhinosinusitis and cough is still not completely understood, however, direct stimulation of nasal mucosa, upper airway cough syndrome, inflammation of the airways, and cough reflex sensitisation play the crucial role in the pathogenesis of chronic cough.

Purpose The co-occurrence of adenoids and chronic cough is common in children. The goal of this research was to specify changes in cough reflex sensitivity as a result of adenoid tissue removal. Patients and Methods The sample group consisted of 17 children (six boys and 11 girls, aged 4–12 years, mean age 6.24 years), all of them possessing symptoms of chronic cough and adenoids, confirmed by nasal fiberoptic endoscopy. This sample group underwent cough reflex sensitivity assessment, which took place both prior to and after endoscopic adenoidectomy. The definition of the cough reflex sensitivity is the lowest capsaicin concentration that caused two (C2) or five (C5) coughs. Capsaicin aerosol in ascending concentrations (from 0.61 to 1250 µmol/L) was inhaled by a single-breath method (KoKo DigiDoser), with the addition of an inspiratory flow regulator valve (RIFR). Results Concentrations of capsaicin causing two (C2) and five coughs (C5) were reported. Cough sensitivity (geometric mean with 95% CI) for C2 was 31.86 (12.98–78.18) µmol/L preoperatively and 11.97 (6.16–23.26) µmol/L postoperatively ( P =0.064). Cough sensitivity for C5 was 234.91 (97.19–567.77) µmol/L preoperatively and 69.13 (29.08–164.35) µmol/L postoperatively ( P =0.022). The children’s pulmonary function was within the normal range. Conclusion In our study, adenoidectomy significantly increased cough reflex sensitivity in non-atopic children suffering from chronic cough.